A project is proposed which plans to investigate the mechanism of action of vitamin E on platelet aggregation, release and adhesivity and determines the in vivo effect of alpha-tocopherol on these platelet functions. These objectives present a continuation of our previous studies in this field which proved vitamin E to be an effective in vitro inhibitor of platelet aggregation and release. Preliminary studies of its mechanism of action suggested a direct influence of vitamin E on the fluidity of platelet membranes. In addition, as alpha-tocopherylquinone was found to posses almost equally potent inhibitory activity as the free alcohol form of the vitamin, we suspect a direct physicochemical interaction between arachidonic acid and alpha-tocopherol in accordance with the hypothesis of Lucy and Diplock. This hypothesis which forms the rationale of our approach implies that vitamin E would make arachidonic acid unavailable for oxidative conversions by cyclooxygenase and lipoxygenase. As a further consequence we expect potentiation of a vitamin E effect on platelet aggregation by the usual anti-inflammatory agents. Specifically we propose to study the effect of vitamin E on physicochemical and biological properties of platelet membranes. To investigate the former, platelets or liposomes prepared from their membrane lipids will be labeled with diphenyl-hexatriene and its fluorescence polarization evaluated as a function of temperature. Adenylate cyclase, phospholipase A2, serotonin and glucose transport and Na ion and K ion flux are the other parameters which will be assayed in normal and vitamin E-enriched human platelets and in vitamin E-deficient rat platelets. To verify the physiochemical interaction of arachidonic acid with vitamin E, its effect and that of phytol and similar compounds on the aggregation-induced conversion of arachidonic acid will be examined. Finally the in vivo effect on platelet function of vitamin E supplementation alone and in conjunction with aspirin will be evaluated in a group of normal volunteers. These studies have an obvious practical implication as vitamin E is one of the few physiological anti-aggregants. In addition the projected studies will give us valuable information on the physiological role of this vitamin in platelets.